The oral microbiome is an important component of systemic health. Many oral bacterial species are associated with oral, as well as systemic diseases. Periodontal disease (PD) is a common condition characterized by a chronic inflammatory response to certain types of bacteria that destroys the supporting structures of the teeth. PD has been associated with other systemic diseases, particularly diabetes. Adults with diabetes are at higher risk of PD and, in turn, PD disease exacerbates glycemic control and diabetic complications. Both periodontal disease and diabetes have been associated with increased risk of cardiovascular disease (CVD). Previous work using the Coronary Artery Calcification in Type 1 Diabetes (CACTI) cohort at the University of Colorado demonstrated that self-reported PD duration was significantly associated with progression of coronary artery calcification in subjects with type 1 diabetes (T1D), but not in subjects without diabetes. These results suggest that the simultaneous presence of PD and T1D may accelerate CVD processes. The central hypothesis of this project is that oral pathogens are significantly associated with both T1D and subclinical CVD and act to modify the association between these diseases. As such, the objective of this project is to characterize the subgingival microbiome in T1D and to investigate longitudinal relationships between the subgingival microbiome, inflammation, T1D, and subclinical CVD. The long-term goal is to elucidate the biological mechanisms that are involved in the relationships between oral and systemic health. The rationale for this project is that increasing understanding of these relationships and mechanisms could lead to therapies targeted at the oral cavity that would have systemic benefits. We will test our central hypothesis with three specific aims: 1) Identify taxonomic and functional profiles of the subgingival microbiome associated with T1D and PD; 2) Determine the associations between the subgingival microbiome and subclinical CVD in those with and without T1D; 3) Determine whether inflammation acts as a mediator between the subgingival microbiome and subclinical CVD. We will utilize passive drool samples and subgingival plaque collected from CACTI participants to perform 16S ribosomal RNA sequencing of the subgingival microbiome and to measure salivary inflammatory cytokines. The approach is innovative because we are able to comprehensively examine correlates, mediators, and diabetes-specific effects of the relationship between the subgingival microbiome and subclinical CVD. Despite studies showing associations between PD, T1D, and CVD, no work to date has described the subginigval microbiome associated with T1D or has focused on the relationships between these three diseases at the level of the subgingival microbiome. This research is significant because these diseases afflict a large proportion of the population and increased understanding could lead to improved therapies.